Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease

Lucijan Mohorovic,Djulija Malatestinic,Anna M Lavezzi,Sanja Stifter,Vladimir Micovic,Oleg Petrovic,Eris Materljan,Herman Haller,George Perry

doi:10.4236/abb.2014.51003

Lucijan Mohorovic, Djulija Malatestinic + Show 7 more

Open Access

https://doi.org/10.4236/abb.2014.51003

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Abstract

Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer’s disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe2+) iron, or ferric (Fe3+) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as “Brain rust”. Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases.

Highlights

The mechanisms responsible for redox-active iron accumulation in some regions of the brain in Alzheimer’s disease (AD) are unknown, nor if it is an initial event that causes neuronal death or a consequence of the disease process
The present standpoint derived from literature and proper research results showed that continuous exposure to inhaled toxic substances in addition to oxidants by food, water, drugs and their associated cummulative effects, causes increased oxidative stress
It postulates the role of environmental toxic factors on the endothelial small vessels of the brain, increasing the rate of endothelial cell apoptosis and making possible the transport of methemoglobin and heme derived ferric iron across the bloodbrain-barrier (BBB), and its accumulation in the brain parenchyma

Summary

Introduction

The mechanisms responsible for redox-active iron accumulation in some regions of the brain in Alzheimer’s disease (AD) are unknown, nor if it is an initial event that causes neuronal death or a consequence of the disease process. Our goal is to understand iron-induced oxidative stress and point out the deleterious effects of redox-active ferric iron as a final product from methemoglobin and heme degradation. Ferric iron has a direct impact on capillary brain endothelial structure and function and in consequence of apoptosis brain parenchyma atrophy follows, so pinpointing specific clinical determinants for the onset and progression of AD. Ferric-Iron Brain Accumulation as a Cause of Neurodegenerative Brain Disease: A New Insight in Understanding the Mechanism of Iron Transport. Mohorovic et al / Advances in Bioscience and Biotechnology 5 (2014) 12-18 tabolic synergy of nitrogen oxides such as oxidants (RNS) and sulfur dioxide metabolites (RSS) as inhibitors of thiol antioxidants [1]

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